Magnetic Resonance Imaging (MRI) at high field strengths is a n invaluable tool for non-invasively studying brain structure and function in clinical populations. Higher magnetic fields provide greater signal to noise and increased contrast in functional MRI (fMRI). For example, the use of fMRI is crucial for understanding the neural mechanisms underlying reward processing and decision-making, which are likely to be associated with an increased risk of drug abuse. Understanding the altered brain circuitry in populations with drug dependencies is vital to finding effective, lasting treatments. Although it has now possible to use MRI at high fields to investigate neural circuitry and brain structure in clinical research, these studies are severely hampered by critical methodological limitations including magnetic susceptibility artifacts and RF field inhomogeneity. Susceptibility artifacts produce signal loss in many key brain regions such as the ventral striatum, amygdala, orbitofrontai cortex, basal ganglia, and nucleus accumbens. All of these regions are vital to understanding reward and addiction as well as numerous other neuropsychiatric disorders. Furthermore, the high fields needed for improved fMRI contrast also produce large image intensity variations and artifacts associated with the wavelike behavior of the RF field. These problems become worse as the field strength increases and currently leave ultra-high field scanners such as 7T impractical for clinical use. In the present application, which is a continuation of R21-DA15900, our group of investigators will tackle these technical limitations and develop and validate solutions designed to improve our ability to investigate the brain at high field. Specifically, we will design, build, and validate the use sensitivity encoding with multiple transmitters (XSENSE) to create practical implementations of tailored RF pulses at 3T. The tailored RF pulses will be used to shape MRI excitations, producing slices with improved homogeneity and less signal loss. We will combine parallel transmission with parallel reception for further refinements in image accuracy. Whole brain acquisitions for fMRI and structural MRI will be created and carefully characterized. The fMRI sequence will allow for the imaging of inferior brain regions, making new clinical applications possible. The structural MRI sequence will be robust to RF field inhomogeneity and will be tested at 7T as well. The techniques will be validated and compared in healthy human volunteers and then in an fMRI pilot study of the reward circuit in a population of abstinent drug users and controls. [unreadable] [unreadable] [unreadable]